6FAX

Complex of Human CD40 Ectodomain with Lob 7.4 Fab

6FAX の概要

• エントリーDOI: 10.2210/pdb6fax/pdb
• 分子名称: Lob 7.4 light chain, Lob 7.4 heavy chain, Tumor necrosis factor receptor superfamily member 5, ... (4 entities in total)
• 機能のキーワード: cd40, engineered fab, agonist, mab, immune system
• 由来する生物種: Homo sapiens; 詳細
• 細胞内の位置: Isoform I: Cell membrane; Single-pass type I membrane protein. Isoform II: Secreted: P25942
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 68515.46

構造登録者

Orr, C.M.,Tews, I.,Pearson, A.R. (登録日: 2017-12-18, 公開日: 2018-02-07, 最終更新日: 2024-11-06)

主引用文献

Yu, X.,Chan, H.T.C.,Orr, C.M.,Dadas, O.,Booth, S.G.,Dahal, L.N.,Penfold, C.A.,O'Brien, L.,Mockridge, C.I.,French, R.R.,Duriez, P.,Douglas, L.R.,Pearson, A.R.,Cragg, M.S.,Tews, I.,Glennie, M.J.,White, A.L.
Complex Interplay between Epitope Specificity and Isotype Dictates the Biological Activity of Anti-human CD40 Antibodies.
Cancer Cell, 33:664-675.e4, 2018

PubMed Abstract: Anti-CD40 monoclonal antibodies (mAbs) that promote or inhibit receptor function hold promise as therapeutics for cancer and autoimmunity. Rules governing their diverse range of functions, however, are lacking. Here we determined characteristics of nine hCD40 mAbs engaging epitopes throughout the CD40 extracellular region expressed as varying isotypes. All mAb formats were strong agonists when hyper-crosslinked; however, only those binding the membrane-distal cysteine-rich domain 1 (CRD1) retained agonistic activity with physiological Fc gamma receptor crosslinking or as human immunoglobulin G2 isotype; agonistic activity decreased as epitopes drew closer to the membrane. In addition, all CRD2-4 binding mAbs blocked CD40 ligand interaction and were potent antagonists. Thus, the membrane distal CRD1 provides a region of choice for selecting CD40 agonists while CRD2-4 provides antagonistic epitopes.

PubMed: 29576376
DOI: 10.1016/j.ccell.2018.02.009

実験手法

X-RAY DIFFRACTION (2.99 Å)